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工程化单克隆抗体重组单链可变片段为感染H9N2禽流感的鸡提供保护。

Engineered Recombinant Single Chain Variable Fragment of Monoclonal Antibody Provides Protection to Chickens Infected with H9N2 Avian Influenza.

作者信息

Lukosaityte Deimante, Sadeyen Jean-Remy, Shrestha Angita, Sealy Joshua E, Bhat Sushant, Chang Pengxiang, Digard Paul, Iqbal Munir

机构信息

The Pirbright Institute, Pirbright, Woking GU24 0NF, UK.

The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.

出版信息

Vaccines (Basel). 2020 Mar 3;8(1):118. doi: 10.3390/vaccines8010118.

Abstract

Passive immunisation with neutralising antibodies can be a potent therapeutic strategy if used pre- or post-exposure to a variety of pathogens. Herein, we investigated whether recombinant monoclonal antibodies (mAbs) could be used to protect chickens against avian influenza. Avian influenza viruses impose a significant economic burden on the poultry industry and pose a zoonotic infection risk for public health worldwide. Traditional control measures including vaccination do not provide rapid protection from disease, highlighting the need for alternative disease mitigation measures. In this study, previously generated neutralizing anti-H9N2 virus monoclonal antibodies were converted to single-chain variable fragment antibodies (scFvs). These recombinant scFv antibodies were produced in insect cell cultures and the preparations retained neutralization capacity against an H9N2 virus in vitro. To evaluate recombinant scFv antibody efficacy in vivo, chickens were passively immunized with scFvs one day before, and for seven days after virus challenge. Groups receiving scFv treatment showed partial virus load reductions measured by plaque assays and decreased disease manifestation. These results indicate that antibody therapy could reduce clinical disease and shedding of avian influenza virus in infected chicken flocks.

摘要

如果在接触各种病原体之前或之后使用,用中和抗体进行被动免疫可能是一种有效的治疗策略。在此,我们研究了重组单克隆抗体(mAb)是否可用于保护鸡免受禽流感感染。禽流感病毒给家禽业带来了巨大的经济负担,并对全球公共卫生构成人畜共患感染风险。包括疫苗接种在内的传统控制措施不能提供对疾病的快速保护,这凸显了需要采取替代的疾病缓解措施。在本研究中,先前产生的中和抗H9N2病毒单克隆抗体被转化为单链可变片段抗体(scFv)。这些重组scFv抗体在昆虫细胞培养物中产生,并且制剂在体外保留了对H9N2病毒的中和能力。为了评估重组scFv抗体在体内的功效,在病毒攻击前一天和攻击后七天用scFv对鸡进行被动免疫。接受scFv治疗的组通过噬斑测定法测量显示部分病毒载量降低,并且疾病表现减轻。这些结果表明,抗体疗法可以减少感染鸡群中禽流感病毒的临床疾病和排毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c994/7157677/4be521bc7164/vaccines-08-00118-g001.jpg

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